SCIENTIFIC EXPERTISE IN ONCOLOGY AND BONE DISEASES
Over 20 years of experience in leading biomedical research and business.
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Summary of ECTS 2024 Annual Meeting and advantages of small-animal DXA in accelerating preclinical research

OncoBone attended the European Calcified Tissue Society (ECTS) Annual Meeting on May 25-28 in Marseille, France. The event covered main areas in basic and clinical research and provided opportunities for scientists to network and share their research. Interesting research areas for OncoBone included osteoimmunology, basic research sessions discussing interactions between bone and immune cells, and rare bone diseases that has been an upcoming field of research in recent years.

OncoBone is a distributor of small-animal DXA iNSiGHT in Europe. In ECTS, OncoBone presented a poster titled: ‘Dual-energy x-ray absorptiometry (DXA) differentiates body composition and bone mineral density in different mouse strains’. Below is a summary of what we presented in the poster.

Imaging methods in bone and metabolic research

Widely used imaging methods include Dual-energy X-ray Absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and micro-computed tomography (µCT) in bone research, and DXA and nuclear magnetic resonance (NMR) in metabolic research. These methods have different advantages, and it can be challenging to choose the right methods for a study. DXA technology utilizes variable absorption of X-rays by different body components that allows reliable analysis of body composition and bone mineral density (BMD). DXA is the gold-standard bone analysis method in humans, but its full potential has not been exploited in preclinical studies. In recent years, DXA has been considered more for preclinical studies as it allows fast scans with high precision and accuracy, multiple imaging sessions per study, and user-defined Region Of Interest (ROI) -based analysis.

Validation of DXA in small animals

In validation of the small-animal DXA iNSiGHT, body composition and BMD were analyzed in three different mouse strains, C3H, C57BL6 and BALB/c. C3H mice had the highest BMD, body weight, fat and lean mass. The DXA results correlated with more detailed bone analysis with µCT and bone histomorphometry. We conclude that mouse strains have variable body composition and BMD, which can affect study outcome, and rapid whole-body imaging and ROI analysis are the main advantages of DXA.

iNSiGHT DXA: Precision, accuracy and easiness of analysis

Non-invasive iNSiGHT DXA has fast scanning time, minimal radiation exposure for small animals, and radiation-free environment for researchers. It offers an optimized method for in vivo imaging of small animals and allows longitudinal studies with repeated scannings. iNSiGHT DXA has higher precision (CV<1%) and accuracy (R²>0.9) than those of NMR and µCT. iNSiGHT DXA presents ultimate high-resolution images of 100 μm, and even higher 30 µm resolution with 4x magnification in digital radiography (DR) mode. DR imaging and Color Mapping for lean and fat distribution are optimized for visual analysis and assessment. User-defined ROI-based analysis with multiple areas allows researchers more flexibility and more precise analysis in their research.

Key features of iNSiGHT include:

  • Easy to use
  • High precision and accuracy
  • Fully shielded cabinet safe for users
  • Longitudinal measurements in anesthetized animals
  • Safe low-dose radiation, allowing repeated measurements

If you are interested to learn more, please contact us at info@oncobone.com.

CDMO services for small molecules

OncoBone has partnered with a small-molecule CDMO service provider to expand its drug development service offering. Below you can find more information about the services, and you can request additional information by reaching info@oncobone.com.

Scope of the CDMO offering

The partner CDMO of OncoBone has been a trusted provider since 2001. They operate in 3 000 m2 modern facilities including an R&D laboratory, GMP pilot manufacturing units, final handling and analytical laboratories. They are specialized in process chemical R&D services and cGMP manufacturing of small-molecule Active Pharmaceutical Ingredients (APIs) for early-stage drug development including preclinical and phase 1 and 2 clinical studies.

Key service areas of the partner CDMO are described below in Figure 1. They operate both with new chemical entities (NCEs) and generic market compounds according to current Good Manufacturing Practice (cGMP) standards. Their facilities are inspected regularly by the European Medicines Agency (EMA/FIMEA) and the U.S. Food and Drug Administration (FDA) and by their partners and customers.

Figure 1: Summary of the small-molecule CDMO service offering

Summary of key expertise areas

  • Broad expertise in organic chemistry
    • Experienced personnel for resolving complex chemical problems
    • Process R&D, scale-up and optimization
  • Routinely inspected by regulatory authorities and customers
    • Last EMA audit in 2021, next FDA audit to be performed in 2023
    • Customer audits annually
  • Small, flexible company with highly motivated personnel
    • Focus on quality and timely delivery
    • Open personal level communications

If you are interested to learn more, please contact us at info@oncobone.com.

Use cases of Dual-energy X-ray Absorptiometry (DXA) in analyzing bone and body composition

OncoBone is a distributor of small-animal DXA iNSiGHT in Europe.

Basics of DXA technology and its use in bone and metabolic diseases

DXA (Dual-energy X-ray Absorptiometry) is a measurement technology based on variable absorption of high and low energy X-rays by different body components, allowing fast and reliable analysis of bone, soft and fat tissues. iNSiGHT DXA is a fully shielded body composition analyser for small laboratory animals such as rodents that offers fast scanning time, high-resolution images and user-specified multiple ROI analytics with ultimate precision and accuracy.

Non-invasive iNSiGHT DXA has overcome the limitations of conventional methods by fast planar imaging, minimal radiation exposure and radiation-free environment for researchers, offering a novel optimized method for in vivo imaging of small animals that allows longitudinal investigations with repeated scannings in long-term studies. iNSiGHT has been widely used in bone and metabolic diseases. Below is a summary of two recent publications where iNSiGHT has been used.

Read more about iNSiGHT small-animal DXA here.

Case example 1: Analysis of sarcopenia in experimental colitis model

The study evaluated the effects of a IL-12/23 neutralizing antibody in sarcopenia. The researchers used dextran sulfate sodium to induce colitis. During the colitis induction phase, IL-12/23 neutralizing antibody was given to the mice at days 3 and 5, and the study lasted a total of 8 days. Body composition was analyzed by iNSiGHT DXA at the end of the study.

The study results indicated that IL-12/23 neutralizing antibody suppressed colitis in the model and helped to maintain muscle mass and improve muscle function. DXA analysis revealed decreased fat and lean mass together with decreased body weight in a control group with colitis receiving vehicle compared to healthy mice or mice with colitis treated with IL-12/23 neutralizing antibody. You can find the full research publication from the following link:

Jung YK, Lee S, Yoo JI, Baek KW. The protective effect of IL-12/23 neutralizing antibody in sarcopenia associated with dextran sulfate sodium-induced experimental colitis. J Cachexia Sarcopenia Muscle. 2023 Apr;14(2):1096-1106. doi: 10.1002/jcsm.13208. Epub 2023 Mar 5. PMID: 36872597; PMCID: PMC10067489.

Case example 2: Analysis of bone parameters in different mouse strains with different metabolic activity

The study evaluated bone remodelling in three mouse stains, C3H, BALB/c and C57BL6, with different fat and lean masses. C3H mice had the highest body weight together with the highest fat and lean mass as determined by DXA, followed by C57BL6 and BALB/c mice. Bone mineral density (BMD) and bone mineral content (BMC) measured by DXA indicated similar findings, demonstrating that C3H mice with highest body mass had also highest BMD and BMC values, followed by C57BL6 and BALB/c mice. The DXA results correlated with more detailed analysis of bone analyzed with more extensive methods such as µCT and bone histomorphometry.

The study also evaluated effects of ovariectomy and the use of bisphosphonates on bone parameters. If you are interested to learn more about the study, you can find the full research publication from the following link:

Kim MY, Lee K, Shin HI, Lee KJ, Jeong D. Metabolic activities affect femur and lumbar vertebrae remodeling, and anti-resorptive risedronate disturbs femoral cortical bone remodeling. Exp Mol Med. 2021 Jan;53(1):103-114. doi: 10.1038/s12276-020-00548-w. Epub 2021 Jan 12. PMID: 33436949; PMCID: PMC8080628.

Read more about scientific research done with iNSiGHT small-animal DXA here.

If you are interested to learn more about iNSiGHT small-animal DXA, please contact us at info@oncobone.com.

New publication about insights into immuno-oncology drug development landscape on bone metastasis

OncoBone recently published a new review article in the Journal ‘Frontiers in Immunology’. The publication ‘Insights into immuno-oncology drug development landscape with focus on bone metastasis’ was a collaboration with Bioseeker Group and the publication was made possible by using their 1stOncology database for searching novel immunotherapies with effects on bone metastases. The publication summarizes key data of 24 emerging immunotherapies currently evaluated in clinical trials with potential efficacy on bone metastasis.

Bone metastases are an unmet medical need

Metastases are the main cause of cancer-related deaths and bone is among the major sites of metastasis in many cancers such as breast, prostate, lung, renal, colon and bladder cancer and melanoma. Breast and prostate cancer patients are most affected by bone metastases and about 70-90% of advanced stage patients develop bone metastases at end-stage disease. Notably, when bone metastases are observed, the 5-year survival rate drops to 5% as there are no effective treatments available. Bone metastases are incurable and induce severe skeletal-related effects such as pathological fractures, spinal cord compression, bone pain and decreased quality of life.

Immunotherapy development for bone metastasis

Despite the success of immunotherapies in oncology, no immunotherapies are approved for bone metastasis and no clear benefit has been observed with approved immunotherapies in treatment of bone metastatic disease.Bone is a highly immunosuppressed microenvironment, which may explain why immunotherapies have not produced promising effects on bone metastatic patients. We have recently established a novel osteoimmuno-oncology (OIO) concept that refers to interactions between cancer, bone and immune cells. It is essential to understand these interactions in order to develop effective and safe therapies for cancer patients with bone metastases. The OIO concept is supported by years of research on the role of interactions between cancer, bone and immune cells, and also by observations in patients treated with different immunotherapies who developed skeletal-related adverse events (SRAEs) such as resorptive bone lesions, spinal cord compression and even fractures. Therefore, development of novel therapies with confirmed efficacy on bone metastasis and without causing SRAEs should be prioritized especially for bone metastatic patients who already have compromised bone health.

Data search in 1stOncology

The review summarizes current immuno-oncology drug development landscape for bone metastatic breast and prostate cancer. Using 1stOncology, a comprehensive oncology-focused drug development database that contains detailed scientific, clinical and commercial drug information on almost 20,000 oncology drugs and 1,877 targets and covers more than 21,000 interventional clinical trials in 391 indications, we identified drugs with preclinical or clinical data available in the context of bone metastasis.

As a conclusion of the database search we identified and evaluated 24 therapies in development that are described in more detail in the review.

Summary of the main findings

  • Bone metastasis drug development is variable, including different treatment modalities, treatment routines, inclusion and exclusion criteria for patients and follow-up of tumor response
  • The treatments that we evaluated to be most promising are related to targets with close connection to tumors growing in bone metastatic microenvironment, and their clinical evaluation followed outcomes in bone metastatic patients
  • We also identified cases where a therapy showed promising efficacy on breast cancer bone metastasis but no effects in prostate cancer bone metastasis, demonstrating the difference between tumor types
  • Only a few of the identified therapies were tested, or had published data available, in appropriate preclinical bone metastasis models to support the decision to move forward to clinical trials including patients with bone metastases
  • Guidance on how to study and evaluate effects of therapies on bone metastases in clinical trials should be established to provide more concrete guidance on how to evaluate anti-cancer effects on bone metastasis by utilizing imaging and biomarker strategies
  • Publication strategies of drug development companies heavily depend on intellectual property rights. Therefore, studies are often published during later development phases and different data sources and databases are important tools to follow real-time drug development

Please read the full text from the following link:

Kähkönen et al., Insights into immuno-oncology drug development landscape with focus on bone metastasis, Front. Immunol., Volume 14, 2023

For more information about 1stOncology, please visit https://www.1stoncology.com/, and additional information in https://www.bioseeker.com/.

If you are interested to learn more about the topic, please reach out to info@oncobone.com.

Virtual CRO concept development project completed

At the end of 2022 OncoBone received funding from Centre for Economic Development, Transport and the Environment (ELY Centre) for developing a Virtual CRO concept as a new business model. The project was co-funded by European Regional Development Fund of the European Union. This blog post summarized the outcome of the project and the Virtual CRO concept as a new business concept for OncoBone.

Background of the project

Founders of OncoBone have a long history in working in preclinical CRO business and a good understanding of the business. This expertise has been valuable in working with clients globally since the establishment of OncoBone in 2020.

The idea of the Virtual CRO concept was initiated in discussions with a US-based client who was looking for a partner to coordinate their preclinical studies. They had no experience in how to plan, execute, manage or report results of such studies. OncoBone started the work by providing scientific expertise for the planned studies, but soon it became clear that multiple CRO and other partners were needed to carry out all planned studies. In discussions with the client, it was found easier if OncoBone would have responsibility in managing all the partners, including communicating with and managing all the partners, preparing business agreements and reporting back to the client on a timely manner. These discussions and ideas were the basis of the Virtual CRO concept.

Virtual CRO concept

In this project, the original idea of the Virtual CRO concept was modified to a general business concept. In the Virtual CRO concept, OncoBone will sign an agreement with a pharma/biotech company for acting as their Virtual CRO. OncoBone will then outsource all laboratory work to mutually selected partner CROs and sign agreements with them for their part of the work.

OncoBone will manage the study on behalf of the client and regularly update the client about study progress. The client will approve the Agreements, Study Protocols and Final Reports before they are finalized with the partner CROs. OncoBone will be the only point of contact for the client during the study, and fully responsible to the client for the whole project, while the partner CROs will be responsible for their parts of the work to OncoBone.

Figure 1: Interactions of OncoBone as the Virtual CRO with the client and the partner CROs

The Virtual CRO concept has been well received and there are currently many projects ongoing under the business concept. We are grateful to our current clients for their trust in us managing their projects.

Expanding the partner CRO network

Based on their professional background, founders of OncoBone have a large network of CRO companies globally. OncoBone’s strongest fields of expertise include oncology and bone diseases, where the founders have done most of their work during their academic training and corporate careers. However, the Virtual CRO concept can be applied to any indication because its core function is to assist in managing preclinical studies, and the same basic principles are followed regardless of the disease indication.

During the project, OncoBone included new CRO partners to its network, allowing to better serve clients with various needs for preclinical studies. Also, discussions with potential new partners are constantly ongoing. If your CRO company would be interested to join our partner CRO network, please contact info@oncobone.com to learn more.

Establishment of quality assurance and audit systems

One of the issues raised in discussions with pharma/biotech clients during the project was related to qualifying CROs. In the future, OncoBone will visit its key CRO partners regularly and audit them according to an auditing system that was established in this project with the help of an expert consultant with decades of experience in auditing. By regular audits, OncoBone can ensure to its future pharma/biotech clients that the partner CROs are conducting high quality research.

If you are interested to learn more about the Virtual CRO concept of OncoBone and how it could be of help in your business, please reach out to info@oncobone.com to learn more.

CRDMO services with Professional Microbial Expression System

OncoBone has partnered with a global leading CRDMO service provider to complement its drug development service offering. Below you can find more information about the service, and you can request additional information by reaching info@oncobone.com.

What is a CRDMO?

CRDMO stands for Contract Research Development and Manufacturing Organization. The partner CRDMO of OncoBone has special expertise in microbial expression systems and the work for example with recombinant proteins/polypeptides, nanobodies, gene therapies, nucleic acid drugs and novel recombinant vaccines. The scope of their business covers one-stop chemistry, manufacturing and controls (CMC) services throughout the entire drug lifecycle, including for example engineering bacteria construction, strain bank establishment, lab scale process development and optimization, pilot process scale-up and production, clinical sample preparation, quality specification establishment, analytical method development and validation, compliant production (GMP), quality management system establishment and registration application.

Figure 1: Overview of CRDMO service covering.

Scope of the CRDMO offering

The partner CRDMO utilizes a Professional Microbial Expression System to manufacture products in the following categories:

  • Recombinant proteins and polypeptides
    • Services from strain bank construction, process and analytical method development and cGMP production to aseptic filling of drug products
    • Supporting recombinant polypeptides/proteins, recombinant antibodies (antibody fragments) and recombinant vaccines (VLP) etc.
  • Nanobodies
    • E.coli prokaryotic expression, eukaryotic expression and mammalian cell expression systems
    • Monovalent, bivalent and trivalent nanobodies
  • Polypeptide nucleic acid drugs
    • Process development from sequence design and optimization, gene synthesis, in vitro transcription, purification and mRNA quality control
    • Pre-made/customized RNA products
    • Supporting mRNA, CircRNA, etc.
  • Cell and gene therapy polypeptides
    • Different levels of plasmids such as non-GMP, GMP-like and GMP according to client’s requirements, to meet the needs of different phases of research, IND registration and application, clinical research and commercial production

Drug substance production capabilities

Through the partnership OncoBone can provide our clients services for preclinical, clinical and marketed drug production in a one-stop shop manner. There are five production lines of drug substance designed based on quality by design (QbD) and in compliance of GMP requirements of FDA and EMA, which can provide bioreactors at various sizes of 50-100 L, 200 L, 500 L, 1,000 L and 2,000 L to support production needs of our clients at different stages of development.

Relying on international advanced production equipment, flexible production line configuration and high standard quality systems, the new drug development process of the clients can be efficiently promoted.

Service highlights include:

  • Industrial scale guarantee
    • Production services of drug substances at a scale of 50-100 L, 200 L, 500 L, 1,000 L, and 2,000 L to meet the needs of different projects
  • Rich technology transfer experience
    • Comprehensive and perfect technology transfer process and risk control system
  • Compliance assurance
    • Well-established quality management system in compliance with the requirements of FDA and EMA, and an experienced quality management team

Quality Control System

High quality of the CRDMO service is ensured with a high GMP quality management system, providing clients continuous and stable quality services through close co-operation between the quality control (QC), production and quality assurance (QA) teams in testing raw materials and excipients, intermediate process controls, stability studies and product release testing of biological drug products. The certified QC system is in compliance with regulatory requirements throughout all phases of QC testing.

Service features include:

  • Equipped with advanced quality analysis testing instruments
  • The QC team has undergone strict GMP training and guidance and is familiar with newly revised GMP requirements
  • Skilled in physical, chemical, biological and microbiological QC testing methods
  • Rich experience in project execution
  • In addition to current scopes, the testing capabilities continue to be expanded

Overview of globalized registration and application services

High-quality, efficient and accurate registration support is provided by an extensive drug registration and application team, including domestic and international IND/BLA application services. The comprehensive registration and application services include CMC consulting services, guidance on registration and application strategy, assistance in completing writing and submission of CMC-related CTD documents, assistance in communication with official agencies, guidance on site verification for development and research, organization of drug registration regulations training and conference guidance, etc.

If you are interested to learn more, please contact us at info@oncobone.com.

Fast, precise and accurate analysis of Body Composition in small animals by Dual-energy X-ray Absorptiometry (DXA)

OncoBone is a distributor of small-animal DXA iNSiGHT in Europe.

DXA technology: Gold Standard for body composition analysis

DXA (Dual-energy X-ray Absorptiometry) is a measurement technology that is based on variable absorption of X-rays by different body components. DXA uses high and low energy X-ray photons that are differentially absorbed by different tissue types, including bone, soft and fat tissues. DXA measurements distinguish bone from soft tissues due to higher number of calcium and phosphorous atoms in bone compared to carbon, nitrogen and oxygen atoms in soft tissues. Fat is largely composed of repeated methylene units ((CH2)n), whereas X-ray attenuation of lean tissues is similar to water (H2O). The difference in X-ray attenuation between fat and lean tissues is attributed to the atomic number difference between carbon and oxygen.

iNSiGHT DXA: Body Composition Analyzer for small laboratory animals

iNSiGHT DXA is a fully shielded body composition analyser for small laboratory animals such as rodents. It offers fast scanning time, high-resolution images and user-specified multiple ROI analytics with ultimate precision accuracy. iNSiGHT allows total and regional assessment for longitudinal in vivo follow-up of these compartments.

iNSiGHT allows accurate separation of fat, lean and bone mass (g) and their ratio (%) in specific ROIs as well as in total body.

iNSiGHT can be widely used in musculoskeletal and metabolic diseases

Traditional bone, fat and body composition analysis

Invasive methods requiring animal sacrifice and post-mortem studies have traditionally been used for determining bone and fat parameters and body composition in small animals. For bone parameters such methods include µCT, histomorphometry, biomechanical testing and ash weight analysis. µCT can also be used non-invasively in vivo, but it involves long-term X-ray exposure that restricts repeated scannings in vivo and use in longitudinal studies. Another method that can be used for adipose tissue analysis in rodents is NMR, which involves prohibitive costs and long acquisition times. Rapid, quantitative and non-invasive alternatives are therefore desirable.

iNSiGHT DXA: Precision, accuracy and easiness of analysis

Non-invasive iNSiGHT DXA has overcome the limitations mentioned above by fast planar imaging, minimal radiation exposure, and radiation-free environment for researchers, offering a novel optimized method for in vivo imaging of small animals that allows longitudinal investigations with repeated scannings in long-term studies. iNSiGHT DXA has proven much higher precision (CV<1%) and accuracy (R²>0.9) than those of NMR and µCT. iNSiGHT DXA presents ultimate high-resolution images of 100 μm, and its magnification shelf supports high-end image analysis of up to 4-fold magnification for X-ray imaging (DR images). DR imaging and Color Mapping for lean and fat distribution is optimized for visual analysis and assessment. As pivotal tools enabling a genuine longitudinal study, iNSiGHT is equipped with Multiple ROI settings, allowing researchers more flexibility and more precise analysis.

Key features of iNSiGHT include:

  • Easy to use
  • High precision and accuracy
  • Fully shielded cabinet safe for the users
  • Longitudinal measurements in anesthetized animals
  • Safe low-dose radiation allowing repeated measurements

If you are interested to learn more, please contact us at info@oncobone.com.

Raising mesothelioma awareness

OncoBone was contacted by Mesothelioma Hope to discuss the possibility to help raise awareness of mesothelioma, a rare cancer mainly caused by exposure to asbestos. As oncology is one of OncoBone’s areas of expertise, agreed to write a blog post to highlight the issue for our network.

To our surprise, during the writing process we noted that for example in our home country, Finland, there is not much information available about mesothelioma from the public healthcare sources even though the National Cancer Registry and Cancer Foundation acknowledge that the incidence of mesothelioma is increasing. This increase occurs even though asbestos exposure is a known risk factor and there are precautions taken to protect the persons at most risk.

This was also summarized at National level in Finland in a recent article in Duodecim titled: ‘asbestos-related diseases are still relevant’. You can read the full article in Finnish from the following link: https://www.duodecimlehti.fi/duo14926.

Mesothelioma basics

Malignant mesothelioma is a rare cancer and the only known cause of it is asbestos exposure. Therefore, people such as construction and factory workers are at most risk. Read more about asbestos exposure from the following link: https://www.mesotheliomahope.com/asbestos/exposure/.

Mesothelioma develops within the lining of the lungs (pleural) or abdomen (peritoneal). In rare cases, mesothelioma tumors can grow in the linings of the heart (pericardium) or testes (tunica vaginalis).

Mesothelioma displays distinct symptoms depending on where the tumors first formed. That said, some general mesothelioma symptoms are common among most patients, including fatigue, fever, fluid buildup in the chest (pleural effusions) or abdomen (ascites), loss of appetite and night sweats. Patients whose cancer has not yet spread usually experience mild and vague symptoms and aren’t aware that they’re sick until their cancer is advanced.

Getting an accurate mesothelioma diagnosis from a specialist is the first step in receiving treatment. A tissue or fluid biopsy from the mesothelioma tumor is the only way to confirm diagnosis.

Mesothelioma has four stages of disease from a localized tumor to metastatic disease. In metastatic mesothelioma, palliative care can help patients manage their mesothelioma symptoms and improve their quality of life. The average life expectancy for mesothelioma is 12-21 months with treatment. Seeing a mesothelioma specialist is important to receive a custom treatment plan involving surgery, chemotherapy, radiation and new treatments that help extend life.

Mesothelioma existing and emerging treatment options

The most common mesothelioma treatment options include surgery, chemotherapy, radiation, or a combination of the three. Although there is no cure for mesothelioma, top doctors work closely with their patients and healthcare support teams to develop effective, personalized cancer care plans that reduce symptoms and increase survival time.

Patients diagnosed with mesothelioma may be able to participate in a clinical trial. Mesothelioma clinical trials test upcoming treatments to find ways to help patients live longer. Emerging mesothelioma treatments in clinical trials include anti-angiogenesis drugs, gene therapy and photodynamic therapy.

A therapy called Tumor Treating Fields (TTFields) was approved for use in treating pleural mesothelioma in 2019. The therapy disrupts the cancer’s ability to spread and it is currently used alongside chemotherapy.

Immunotherapy development for mesothelioma has provided some success in recent years. One of the most notable new treatment options for pleural mesothelioma combining two immunotherapy drugs nivolumab (Opdivo®) and ipilimumab (Yervoy®) was approved by the FDA in October 2020. Further, a combination of two other immunotherapy drugs — atezolizumab (Tecentriq®) and bevacizumab (Avastin®) was recently reported to help in peritoneal mesothelioma.

If you are interested to learn more about immunotherapy treatment of mesothelioma, please see the following selected scientific articles:

  • Han Y, Zhang T, Chen H, Yang X. Global magnitude and temporal trend of mesothelioma burden along with the contribution of occupational asbestos exposure in 204 countries and territories from 1990 to 2019: Results from the Global Burden of Disease Study 2019. Crit Rev Oncol Hematol. 2022 Nov;179:103821.
  • Dacic S. Pleural mesothelioma classification – update and challenges. Mod Pathol. 2022 Jan;35(Suppl 1):51-56.
  • Fennell DA, Dulloo S, Harber J. Immunotherapy approaches for malignant pleural mesothelioma. Nat Rev Clin Oncol. 2022 Sep;19(9):573-584.

Disclaimer in Finnish: Yllä esitetty tieto perustuu Mesothelioma Hope -yhdistyksen jakamaan tietoon, jonka oikeellisuus on tarkistettu. Mesoteliooman ilmaantuvuus, elinajanennuste ja saatavilla olevat hoitomuodot saattavat olla erilaiset Suomessa. Mikäli aihe on sinulle ajankohtainen, ole yhteydessä hoitavaan lääkäriisi.

If you are interested to learn more about the issues mentioned in this blogpost, please visit  https://www.mesotheliomahope.com/. You can also reach out to us at info@oncobone.com.

Summary of ECTS 2022

European Calcified Tissue Society (ECTS) Annual Meeting was held in Helsinki, Finland on May 6-10, 2022. In the history of the society, this was the third time that the annual meeting was held in our home country, after 2000 in Tampere and 1980 in Helsinki. The annual meeting gathered basic and clinical researchers to meet in-person for the first time after 2019. OncoBone held an oral presentation in the pre-congress workshop and presented two posters in the event. This blog post summarized our work presented in the event.

Small-animal DXA for bone and metabolic studies

Dual X-ray Absorptiometry (DXA) is the gold-standard technique used in the diagnosis of osteoporosis in patients. During recent years DXA has gained more and more interest also in animal studies, and we wanted to highlight one new small-animal DXA system, iNSiGHT that OsteoSys introduced to the markets a few years ago. OncoBone is a distributor of iNSiGHT DXA in Europe. DXA is also ‘dual’ in this use-field as it can be used for analyzing bone (bone mineral density and content) and body composition (fat and lean mass) in small animals, therefore benefitting both bone and metabolic research in multi-user institutions such as universities.

OncoBone presented a poster in ECTS summarizing key advantages of iNSiGHT DXA over other commonly used imaging devices in bone and metabolic studies, listed in Table 1 below. DXA allows areal analysis of specific regions of interests (ROIs), which can be done quickly and easily multiple times during the study on anesthetized animals. These features were also greatly appreciated by many researchers we discussed with during ECTS. Supporting techniques such as detailed ex vivo µCT imaging of bone architecture can be done to complement the observations.

Predictive in vitro organ-on-chip model of osteoarthritis

OncoBone was invited to give an oral presentation on the pre-congress day workshop in an open forum on ‘osteoarthritis and bone’. The presentation titled: ‘A predictive human 3D cartilage-on-chip model for screening anti-osteoarthritis drugs and medical devices’ was selected based on an abstract that we submitted to the event. The work was done in collaboration with BiomimX, inventor of the used platform technology. The presentation showcased the problem that there has been no physiologically relevant in vitro models for OA, which has created a gap in early preclinical testing of novel anti-OA drugs. The key to produce biologically relevant OA models is to use an excess mechanical stimulus to induce OA-like disease to human cartilage micro-organs. OA development to micro-organs was detected by studying OA-related changes, including degradation of cartilage-related protein and induced inflammation. The developed model can be used to test effects of novel anti-OA drugs or medical devices, and the effects can be compared to standard-of-care compounds that produce a corresponding data obtained from animal studies.

The organ-on-chip model for OA, called uKnee, can be reliably used to address different needs in early drug development. The uKnee model can be used for example as a screening model for lead selection, for assisting in dose selection for animal studies, and for mode-of-action studies. Based on our discussions with clients, there is also interest to use the uKnee model to provide data later during the drug development, for example for selecting the final formulation for clinical studies. The uKnee model itself is very versatile and it can be modified to address different research needs.

Organ-on-chips are a growing area of interest for researchers in different fields. In ECTS, there was a Plenary session and a Meet-the-Expert session dedicated to organ-on-chip technology. During the discussion with the audience, one presenter of the Plenary session also highlighted the organ-on-chip OA model that OncoBone presented in the event.

If you are interested to learn more about the issues mentioned in this blogpost, please contact info@oncobone.com.

Summary of AACR 2022

This year’s American Association of Cancer Research (AACR) Annual meeting was held in New Orleans, USA from April 8 to 13. The event was the first Annual Meeting held in-person after  2019. Due to governmental and travel restriction, there was also a possibility to attend online and listen to streamed content via a virtual platform. The content and structure of the Annual Meeting resembled pre-pandemic meetings comprising on lectures, workshops, poster sessions, exhibition and more. In this blog post we concentrate on new preclinical cancer models, and in accordance with a poster that OncoBone presented in the event, work exploring genetic differences in primary tumors and different metastases.

New preclinical models

In any meeting, our interest is to explore new developments in preclinical models. In this meeting, one work that caught our attention was a bone metastasis model induced by caudal artery injection technique (poster number 6010), a method that we have also discussed (Kähkönen et al., 2019). The caudal artery injection technique was first introduced by a Japanese group (Kuchimaru et al., 2018) and it is especially interesting as it allows cancer cells homing to bone from systemic circulation, which is a commonly accepted approach to produce a bone metastasis model. The work presented in AACR reported establishment of two breast cancer models with exclusive metastasis in the hind limbs in tibia and femur.

The interest in humanized mouse models as a choice of IO models is increasing. A new humanized mouse model defective for mouse FcεRI and FcγIIb genes was introduced (poster number 6026). The mice lacked expression of functional mouse FcγRs and activity of endogenous antibody-dependent cellular cytotoxicity (ADCC). When these mice were engrafted with human hematopoietic stem cells (HSCs) it resulted in higher reconstitution of human immune cells, especially CD19+ B-cells and CD33+ myeloid cells than in other mouse strains used in humanizations. The new humanized mouse model also had increased number of activated T cells and memory T cells. This model could induce tumor growth suppression and rejection caused by IO treatment better than traditional humanized mouse strains.

Humanized PDX models are increasingly used in IO research. One study (poster number 6258) compared gene ontology in humanized and immunodeficient TNBC models, demonstrating that biological processes, cellular components, molecular functions and ribosomal relevant proteins, but not immune related genes, were more upregulated in the humanized TNBC PDX model than in the  immunodeficient model.

Bone marrow immune microenvironment contributes to dormancy and activation of disseminated tumor cells (DTCs) in bone metastasis. One study (poster number 5985) compared bone marrow samples from mice with and without bone metastases and intact animals. Mice with bone metastases had lower number of T and B cells in the bone marrow than intact mice, indicating that acquired immunity was diminished in the mice with bone metastases. This also aligns with results we have previously reported in AACR Annual meeting, showing a very low number of T cells in bone metastatic tumor microenvironment (Kähkönen et al., 2018). An increased number of immunosuppressive cells was also observed in the bone marrow of mice with bone metastases, leading to development of immunosuppressive microenvironment, promoting growth of bone metastases.

In summary, new developments in oncology drug discovery and development create a need for more predictive preclinical models for supporting the activities. There have been two important advancements in this area, development of models that recapitulate the disease progression and metastasis, and more advanced immunocompetent models with more complete functional human immune system. These advancements substantially increase clinical predictivity of preclinical work.

Genetic profiles in primary tumor and different metastasis

In AACR Annual meeting, OncoBone presented a poster titled: “Identification of genetic signatures in bone metastasis of breast and prostate cancer”. The work summarizes novel genetic changes expressed in bone metastasis of breast and prostate cancer. The data was obtained from a dataset of 500 metastatic solid tumors, including metastasis-specific biopsy data (Robinson et al., 2017). Genetic alterations in bone metastasis and in other than bone metastasis were compared to identify genetic alterations that would be increasingly or exclusively expressed in bone metastasis. The study identified 8 genes in breast cancer and 3 genes in prostate cancer that were significantly different between the cohorts. Of these, 4 genetic alterations in breast cancer and 1 in prostate cancer showed a significant difference on patient survival in larger cohorts.

Also, other studies presented in AACR underlined the genetic difference in primary tumors and metastases. One study (poster number 5983) reported differences in breast cancer and related lung, liver and brain metastases. High tumor heterogeneity was observed between samples and between different metastases. The five most mutated genes were mostly different in primary tumors and metastases, with some exceptions such as TP53 that was mutated in all samples. Lung and brain metastases were most different from primary tumor. Tumor mutational burden (TMB) was highly different between the primary tumors and metastases.

One study (poster number 5134) reported differences between matched primary and metastatic colorectal tumors. The most common site of metastasis was liver (about 70%) followed by low rates of ovarian and peritoneal metastases. There was a high concordance in the mutational landscape and 80% of the 20 most commonly observed genes were shared between the primary and metastatic tumors. There was also a high heterogeneity between the samples, and some metastatic locations seemed to harbor mutations that were not observed in the primary tumor or in other metastatic locations. TMB was comparable between primary tumor and metastatic locations.

In summary, it is great to note that understanding genetic drivers of metastasis has aroused interest in the cancer research society. Based on the studies presented in AACR, it seems obvious that genetic drivers can be different in metastasis, and the metastatic location can strongly affect TMB and increase the heterogeneity in genetic landscape. The more different the metastatic location is from the primary tumor, the more complex these changes seem to be.

If you are interested to learn more about the issues mentioned in this blogpost, please contact info@oncobone.com.

Plan for events in 2022

OncoBone has released the schedule for events and conferences for 2022. Next year will take us to a mix of scientific and partnering events, hopefully some of which will be arranged in-person. From this blog post you may read more on what events we are participating in 2022 and what are our aims and expectations for these events.

Event calendar for 2022

The event year will start by attending Biotech Showcase, an event brings together global investors and biotech innovators. OncoBone will attend the virtual event during January 17-19. Our primary goals in the event are to discuss partnership opportunities and fundraising for OncoBone Ventures.

Two of the events will be held in Helsinki, Finland. First of them is ChemBio Finland on March 30-31 that brings together chemistry and biotechnology professionals from Nordic Countries and Baltic region. OncoBone is attending the event mainly to meet existing contacts and network with new contacts from our home region.

BIO-Europe Spring is planned to be a hybrid event, the virtual part being held on April 4-6, a week after the in-person part that will be held in Basel, Switzerland. Based on our previous experience OncoBone expects BIO-Europe to be a great event to participate for exploring new partnership opportunities.

The leading oncology scientific event American Association for Cancer Research (AACR) Annual Meeting will be held on April 8-13 in New Orleans, LA, USA. The meeting is planned to be arranged in hybrid format to allow everyone interested to participate. OncoBone has submitted an abstract to the event describing our recent findings on genetic changes in breast and prostate cancer bone metastasis. We are delighted to present and discuss our findings with colleagues in the event.

The second exciting event arranged in Helsinki is the European Calcified Tissue Society (ECTS) Congress on May 7-10. ECTS Congress in the leading European event for bone and musculoskeletal research. OncoBone has submitted two abstracts to the event, one describing positioning of Dual-energy X-ray Absorptiometry (DXA) as an imaging device in bone and metabolic research, and the other describing a novel human 3D cartilage-on-chip technology for osteoarthritis drug development. We are delighted to describe advantages of these technologies in the event.

BIO International Convention that will be held on June 13-16 will be one of the highlights of the event year for OncoBone. The format of the event is to be announced later. Depending on the progress made earlier in the year, the main goal in the event will be either partnering or fundraising.  

The American Society for Bone and Mineral Research (ASBMR) Annual Meeting is planned to be held in-person in Austin, TX, USA on September 9-12. OncoBone is planning to submit 1-2 abstracts to the event before the abstract submission deadline in summer, but the contents remain to be finalized. If you would like to publish and present something together with us, we would be happy to evaluate this opportunity.

According to our current plans the event year will end with BIO-Europe arranged on October 24-26 in Leipzig, Germany. The aims for this event will be placed based on other developments during the year.

Meet us and discuss about collaboration opportunities

OncoBone is always available to discuss any collaboration opportunities whether it is during or outside of events. If you happen to be attending the same events, we would be happy to arrange a possibility to meet also face-to-face.

You may contact us at info@oncobone.com.

Applications of iNSiGHT DXA in bone and metabolic research

Dual-energy X-ray Absorptiometry (DXA) is a widely used imaging technique in bone and metabolic research for quantitating bone mineral density (BMD) and body composition in small animals. After a 20-year history in developing devices for clinical use, in 2019 OsteoSys launched their first small-animal DXA that OncoBone is now proud to distribute to European markets. In this blog post, we summarize published scientific data where iNSiGHT has been used in bone and metabolic research.

Precision and accuracy

After its launch in 2019 iNSiGHT has already provided peer-reviewed publications, and the number is constantly increasing.

The first publication by Yeu and colleagues (1) evaluated the precision and accuracy of iNSiGHT DXA in measuring lean and fat mass in rats receiving two different diets. During the 8-week study period and longitudinal follow-up of the changes in lean and fat mass, they detected small CV and high R2 values for total body weight, total body fat mass, and total body lean mass. Their research was able to detect diet-induced changes over the 8-week study period in all parameters listed above.

To determine the ability of DXA to monitor changes in metabolic parameters, Baek and colleagues (2) studied the precision and accuracy of repeated measurements with iNSiGHT DXA and EchoMRI NMR in mice. Accuracy of the devices was determined by comparing the obtained results to tissue weights. Based on the results, fat and lean mass were more accurately determined by iNSiGHT DXA analysis than with the NMR measurements.

With these results it can be stated that iNSiGHT provides a predictive and accurate method for analyzing body composition in longitudinal studies.

Metabolic research – genetic background and environmental effects

Brown adipose tissue is an important regulator of body weight and metabolism. Ko and colleagues (3) studied effects of brown adipocyte -specific deletion of pink1 and observed brown adipose tissue dysfunction and prone obesity, which was determined by increased body weight and fat mass after exposure to high-fat diet.

Hypoxia-related glucose metabolism was studied by Park and colleagues (4) by exposing mice to normoxic or hypoxic conditions. Their results showed that mouse body weight and fat mass were significantly lower in the hypoxic group than in the normoxic group as demonstrated by DXA measurements.

Furhermore, the effects of hypothalamic proopiomelanocortin neurons on obesity have been studied with iNSiGHT (5, 6), demonstrating yet another example where DXA analysis can be utilized.

Bone diseases – osteoporosis and bone loss

Efficacy of Sanhuang Jiangtang tablets to treat type 2 diabetes -related osteoporosis was studied in leptin-receptor deficient (db/db) mice by He and colleagues (7), who observed that db/db-mice had lower BMD and bone mineral content (BMC) than wild-type mice. Furthermore, db/db mice treated with Sanhuang Jiangtang tablets had increased BMD compared to non-treated mice. This was further confirmed by µCT imaging showing inhibition of bone loss after Sanhuang Jiangtang tablet treatment in db/db mice.

Kim and colleagues (8) studied effects of metabolic alterations on bone remodeling. They compared three different mouse strains (BALB/c, C57BL6, and C3H mice) and observed that C3H mice had the highest fat and lean mass. Treating C3H mice with normal BMD with the bisphosphonate risedronate caused enlargement of femoral cortical bones with low BMD and increased fragility. This phenomenon was only observed in mice with normal BMD, not in mice with estrogen deficiency -caused osteoporosis.

Conclusions

After being only a few years in market, iNSiGHT DXA has been already widely used in research and has provided proof for precision and accuracy of the device and its usefulness in studying bone and metabolic diseases.

For additional information

For any enquiries related to the iNSiGHT DXA device, please contact info@oncobone.com.

References:

  1. Yeu J, Ko HJ, Kim D, Ahn Y, Kim J, Lee W, Jung I, Suh J, Lee SJ. Evaluation of iNSiGHT VET DXA (Dual-Energy X-ray Absorptiometry) for assessing body composition in obese rats fed with high fat diet: a follow-up study of diet induced obesity model for 8 weeks. Lab Anim Res. 2019 Jun 24;35:2. doi: 10.1186/s42826-019-0004-2. PMID: 31463221; PMCID: PMC6707430.
  2. Baek KW, Kim JS, Park JS, Kim SJ, Ha YC, Jeong OY, Yoo JI. Validation of Dual Energy X-Ray Absorptiometry and Nuclear Magnetic Resonance in the Analysis of Body Composition in Mice. J Bone Metab. 2020 Nov;27(4):291-299. doi: 10.11005/jbm.2020.27.4.291. Epub 2020 Nov 30. PMID: 33317232; PMCID: PMC7746482.
  3. Ko MS, Yun JY, Baek IJ, Jang JE, Hwang JJ, Lee SE, Heo SH, Bader DA, Lee CH, Han J, Moon JS, Lee JM, Hong EG, Lee IK, Kim SW, Park JY, Hartig SM, Kang UJ, Moore DD, Koh EH, Lee KU. Mitophagy deficiency increases NLRP3 to induce brown fat dysfunction in mice. Autophagy. 2021 May;17(5):1205-1221. doi: 10.1080/15548627.2020.1753002. Epub 2020 May 13. PMID: 32400277; PMCID: PMC8143238.
  4. Park Y, Hwang D, Park H-Y, Kim J, Lim K. Hypoxic Exposure Increases Energy Expenditure by Increasing Carbohydrate Oxidation in Mice. BioMed Research International. 2020 Article ID 6159407, 8 pages.
  5. Lee CH, Song DK, Park CB, Choi J, Kang GM, Shin SH, Kwon I, Park S, Kim S, Kim JY, Dugu H, Park JW, Choi JH, Min SH, Sohn JW, Kim MS. Primary cilia mediate early life programming of adiposity through lysosomal regulation in the developing mouse hypothalamus. Nat Commun. 2020 Nov 13;11(1):5772. doi: 10.1038/s41467-020-19638-4. PMID: 33188191; PMCID: PMC7666216.
  6. Kang GM, Min SH, Lee CH, Kim JY, Lim HS, Choi MJ, Jung SB, Park JW, Kim S, Park CB, Dugu H, Choi JH, Jang WH, Park SE, Cho YM, Kim JG, Kim KG, Choi CS, Kim YB, Lee C, Shong M, Kim MS. Mitohormesis in Hypothalamic POMC Neurons Mediates Regular Exercise-Induced High-Turnover Metabolism. Cell Metab. 2021 Feb 2;33(2):334-349.e6. doi: 10.1016/j.cmet.2021.01.003. PMID: 33535098; PMCID: PMC7959183.
  7. He Q, Yang J, Zhang G, Chen D, Zhang M, Pan Z, Wang Z, Su L, Zeng J, Wang B, Wang H, Chen P. Sanhuang Jiangtang tablet protects type 2 diabetes osteoporosis via AKT-GSK3β-NFATc1 signaling pathway by integrating bioinformatics analysis and experimental validation. J Ethnopharmacol. 2021 Jun 12;273:113946. doi: 10.1016/j.jep.2021.113946. Epub 2021 Feb 26. PMID: 33647426.
  8. Kim MY, Lee K, Shin HI, Lee KJ, Jeong D. Metabolic activities affect femur and lumbar vertebrae remodeling, and anti-resorptive risedronate disturbs femoral cortical bone remodeling. Exp Mol Med. 2021 Jan;53(1):103-114. doi: 10.1038/s12276-020-00548-w. Epub 2021 Jan 12. PMID: 33436949; PMCID: PMC8080628.

What is a Virtual CRO?

In today’s world anything can be virtual – including a Contract Research Organization (CRO). To better serve our existing and new clients OncoBone has launched a new Virtual CRO service. This blog post summarizes the Virtual CRO concept and how it works in practice.

The idea behind the Virtual CRO concept

During the past years many kinds of virtual concepts have been introduced, including virtual meetings, events, audits and many more. In this virtual world, the idea behind the Virtual CRO concept came from valuable feedback from our clients and fruitful discussions with our contacts. In fact, the concept is not new as it has been successfully utilized by some clinical CROs previously.

During the past years OncoBone has worked with many small pharma/biotech companies who have needs in the service areas we cover. One such service is partner search and evaluation, a function that in midsize and big pharma companies is usually taken care of in separate divisions. Identification and evaluation of CROs is a time-consuming exercise, especially if you have not done it before or are not doing it routinely. There is a large variety of CRO partners available globally, and all of them have a unique set of skills and expertise. After working in this specific business area for decades, OncoBone founders have obtained a large network of CRO partners globally and are in a good position to evaluate their capabilities. During our CRO evaluation projects, it has become obvious for us that the evaluation is worth doing. Many times there are substantial differences between CROs for example in price, quality and time from start to completion of projects.

Also, during the past years we have learned that many companies hesitate, and for a good reason, in starting to work in a new unfamiliar disease indication area. As an example, we have worked with clients whose primary indications are for example in CNS or metabolic diseases, and who wished to perform studies in cancer or bone diseases. We have been able to help these clients by guiding them in model selection, identifying and monitoring CROs who perform the practical work, and interpretation of results. We launched the Virtual CRO concept to be able to offer all of these to our clients in one combined service.

How it works and the benefits

In principle, as a Virtual CRO OncoBone works like a traditional CRO. One difference is that our Virtual CRO outsources all laboratory work to other CROs and service providers. Another difference is that traditional CROs typically have their own network of third-party companies that they outsource work to, but with our Virtual CRO, you can select any partner that you wish to participate in the study. We are happy to recommend possible partners, but the client eventually makes the decision.

As a Virtual CRO we are happy to take more responsibility in study planning and interpretation of results. If a study consists of multiple projects with many partners, we are also happy to provide a summary report that will assist in understanding the results in a larger concept and in regulatory filing among other benefits, a service that is not typically offered by most traditional CROs.

OncoBone is looking forward to the exciting new challenges that the Virtual CRO service will bring to us.

For additional information

If you have any questions related to the blog post or to the Virtual CRO concept, please contact info@oncobone.com.

Summary of ASMBR Annual meeting and advances in osteoarthritis research

OncoBone attended American Society for Bone and Mineral Research (ASBMR) Annual meeting 2021 virtually. The event was held in hybrid format including an in-person part in San Diego and an online- part open to all attendees. In the event, OncoBone presented a poster titled: “uKnee: a human osteoarthritic (OA) cartilage-on-chip model for efficacy screening of anti-OA drugs and medical devices” together with one of our CRO partners, BiomimX. This blog post summarizes the ASBMR event, provides references to selected exciting research in the OA field, and summarizes the poster we presented in the event.

ASBMR Annual meeting 2021

ASBMR Annual meeting 2021 was held in hybrid format including a possibility to attend virtually or in-person in San Diego, CA, USA. Most of the attendees were present virtually. The meeting comprised of four days of sessions including event Highlights, Meet the Professor and Cutting-Edge sessions, Oral and Poster presentations, and Networking either in-person or in chat- rooms provided for virtual participants.

Advances in OA research

OA is a prevalent musculoskeletal disease whose prevalence is expected to increase dramatically in the coming years due to population aging. Up to date, molecular mechanisms of OA initiation and progression are not well understood and there are no treatments available to restore degraded cartilage or decelerate disease progression. Luckily, there is a lot of research being conducted in this area both on the development of new therapies and establishing more predictive preclinical models that can enhance the therapy development, three examples of which are provided below.

Target identification by drug repurposing

One approach of finding new therapies can be through repurposing of existing drugs for OA that was presented in a poster presentation by researchers from the University of California. They used transcriptomics for comparing data from two mouse strains either sensitive or resistant to post-traumatic OA and used the data to identify therapeutic targets. Based on these targets, they identified over 60 FDA-approved therapies that could potentially be used for treating OA.

Advanced drug screening model based on organ-on-chip technology

OncoBone presented a poster in collaboration with BiomimX. The poster titled: “uKnee: a human osteoarthritic (OA) cartilage-on-chip model for efficacy screening of anti-OA drugs and medical devices” summarized the uKnee model that is developed and commercially offered by BiomimX. Dr. Paola Occhetta, CEO of BiomimX, describes the company and its business: “BiomimX is an Italian Startup, developer of Beating Organs-on-Chip solutions, able to integrate for the first time 3D mechanical environment characterizing human organs into miniaturized cell culture platforms. uKnee is one of our first models developed and validated in collaboration with worldwide recognized clinical experts in the field.”

Shortly, uKnee is a novel human mechanically active 3D osteoarthritic cartilage-on-chip model. The organ-on-chip technology can recapitulate the human pathology better than traditional cell culture models. What makes uKnee unique compared to other organ-on-chip models is the hyper-physiological mechanical stimulus provided by BiomimX’s proprietary uBeat® technology that mimics the natural movement activity of an adult. According to Dr. Occhetta, “the key advantage of the system is that uKnee enables for the first time to trigger clinically relevant traits of OA in vitro without the need of bombarding the system with supra-physiological doses of inflammatory cytokines. By only modulating 3D mechanical environment, we can mimic traumatic and chronic events happening in the joint during onset of the pathology.” The mechanical stimulus triggers OA-induced changes in primary human articular chondrocytes including enhancement of catabolic and inflammatory responses and switching towards hypertrophic cartilage phenotype characteristic of OA.

uKnee is an advanced tool for screening of novel disease-modifying OA drugs (DMOADs), and its performance has been demonstrated by testing clinically used SOCs and medical devices. The obtained results are consistent with data obtained from animal studies, highlighting the predictive power of the model. “According to our customers and collaborators, uKnee provides an unprecedented solution to study in-depth mechanisms underlying OA pathology and to detect highly specific effects of new leads. uKnee indeed represents a much more precise snapshot of healthy and osteoarthritic human cartilage as compared to currently available simplistic cell culture tools, finally providing high-content data that can be used to better design animal tests and clinical trials”, Dr. Occhetta comments on feedback received on uKnee.

To answer the growing need of new models, BiomimX is developing the uKnee model further. Dr. Occhetta comments on their ongoing R&D activities: “While uKnee currently integrates only the cartilage compartment, we are working towards integration of a full joint-on-chip encompassing also synovial membrane and subchondral bone. We are indeed aware that OA is a pathology of the joint as a whole, and we are working to provide our customers with this level of complexity”.

Close to human – animal models to confirm efficacy of experimental therapies

A research group from New York University of Grossman School of Medicine tested one FDA-approved therapy currently not indicated for OA in a mouse model and in a non-human primate model of OA. The therapy showed great potency by reducing articular cartilage destruction, osteophyte formation and OA pain, and by inducing thickening of subchondral bone. Use of multiple species improves the clinical predictivity of results, especially when results are confirmed in models resembling human diseases such as non-human primate models of OA.

Concluding remarks

ASBMR Annual meeting has always been a pleasure to attend. It brings together scientists in musculoskeletal research to share and discuss latest research. The restriction of the pandemic has hindered this and hopefully the situation allows traveling and attending the next Annual Meeting in person.

For additional information

If you have any questions related to the blog post or preclinical models described in the text, or you would like to receive a copy of the poster, please contact info@oncobone.com.

Osteoimmuno-oncology, a novel concept describing interactions in bone metastasis to guide development of novel therapies

OncoBone contributed to an invited review article to the special issue ‘Cancer Immunology: From Molecular Mechanisms to Therapeutic Opportunities’ in the Journal ‘Cells’, published on June 17, 2021. The review article titled ‘Osteoimmuno-Oncology: Therapeutic Opportunities for Targeting Immune Cells in Bone Metastasis‘ describes the novel concept of osteoimmuno-oncology (OIO) for the first time. OIO highlights the important interactions between bone, immune and tumor cells in cancer bone metastasis. The concept can be utilized as a basis for guiding development of novel immunotherapies for the currently incurable bone metastases.

It is well established that immunotherapies provide a potential treatment option for currently incurable bone metastases. What is not commonly taken into consideration is that bone marrow is an important secondary lymphoid organ with a unique immune contexture. Even at non-disease state immune cells and bone cells interact with each other, bone cells supporting the development of immune cells and immune cells regulating bone turnover. This homeostatic process is disrupted in cancer when tumor cells enter the bone marrow and grow into secondary tumors.

In this review, the novel OIO concept is introduced. OIO refers to interactions between bone, immune and tumor cells in bone metastatic microenvironment. Understanding the interplay between these three separate, but tightly linked compartments is essential when developing novel therapies for bone metastases. Below is a summary of the key points addressed in the review.

Bone metastases are common and cause high mortality in many cancers including some of the most common cancers such as breast, prostate and lung cancer. One compelling approach for providing effective prevention and treatment options for bone metastasis are immunotherapies. It needs to be understood that the metastatic tumor microenvironment is more than tumor and immune cells, and the cells within the metastatic microenvironment greatly affect the growth of metastasis. OIO is based on two well established concepts: osteoimmunology and immuno-oncology that are now combined in OIO to understanding the interactions in cancer bone metastasis. Next, we briefly describe the three concepts separately in chronological order when we consider formation and growth of bone metastases.

Osteoimmunology: Homeostatic regulation of bone turnover

Bone marrow is an important secondary immune organ where immune cells have multiple interactions with bone marrow stromal cells, and they regulate each others function and activity. To highlight this further, at healthy stage about 25% of bone marrow immune cells are myeloid cells, about 10% are lymphocytes, and about 5% are dendritic cells, antigen-producing plasma cells and natural killer cells. Osteoimmunology is an interdisciplinary research field focusing to understand the interactions between the immune and skeletal system at healthy and disease stages.

Multipotent mesenchymal stem cells (MSCs) in the bone marrow can differentiate into bone-forming osteoblasts that later differentiate into osteocytes. The primary function of the osteoblast is to secrete mineralized extracellular matrix, but it has also an important function in regulating hematopoietic stem cell (HSC) niches. Osteoblast interactions with HSCs are important because HSCs differentiate into bone-resorbing osteoclasts. Osteoblasts and osteoclasts are responsible for the regulation of homeostatic balance between bone formation and resorption. Importantly, HSCs are also progenitors of all immune cells. Signals coming from mature osteoblasts are important for lymphoid progenitor cells and generation of mature T and B cells. Furthermore, osteocytes are important for the maintenance of myeloid cells in the bone marrow. As mentioned previously, immune cells regulate the function of bone cells. As examples of this, T cells regulate bone turnover by promoting osteoclastogenesis and bone loss, and B cells regulate development of osteoblasts and osteoclasts and contribute to homeostatic regulation of bone turnover.

This homeostatic regulation is disrupted in bone metastasis, which is shortly described in the next paragraph.

Cancer-induced bone disease: Vicious cycle of bone metastasis

The formation of metastases in a process called metastatic cascade is well established. However, it is often neglected what happens in the microenvironment where the metastases are formed. Cancer cells have a self-promoting effect in bone, which is called the vicious cycle of bone metastasis. In the vicious cycle, tumor cells promote function of bone cells, affecting primarily to either  osteoblasts (sclerotic bone metastases), osteoclasts (osteolytic bone metastases), or both (mixed bone metastases) to disturb the homeostatic regulation of bone and release growth factors that in turn promote tumor growth. These changes then lead to increased risk of fractures, bone pain and decreased quality of life.

When considering treatment options for patients with bone metastases, it is essential to understand that the tumor that was once growing in the primary organ changes during the metastatic process and typically becomes resistant to standard-of-care therapies due to influence of the metastatic tumor microenvironment. For this reason, the discovery of new therapies should take into account the metastatic microenvironment that you wish to treat, and this is highlighted in the context of immunotherapies in bone microenvironment in the next paragraph.

Immuno-oncology: Immune cells in bone metastasis

Tumor cells modulate the immunological contexture in the bone metastatic microenvironment, in most cases leading to immunosuppression and low response rate to different therapies. In fact, most bone metastases have typically low immunogenicity compared to the primary tumor, and therefore they may respond poorly to immunotherapies, which should be considered when targeting bone metastasis with immunotherapies. Currently, immune cells such as T cells (CD4+, CD8+ and Tregs), MDSCs, macrophages, neutrophils and NK cells are targeted for treating bone metastases. Some promising results have been gained in preclinical and clinical research, and effects of all these cell types are discussed in the review separately.

Based on the OIO concept, most interesting targets would be shared within these three compartments, and they could potentially eradicate tumor growth and restore the homeostatic regulation of bone turnover.

To conclude, in order to develop novel therapies for bone metastasis, it is important to understand how the local microenvironment contributes to the regulation of metastasis. OIO provides one means to understand this in the bone microenvironment, and it may reveal completely new therapeutic opportunities for the currently incurable bone metastases.

Full text of the review can be found from the following link.

Working with CROs – lessons to learn from the webinar

OncoBone co-presented in a webinar titled ‘Working with CROs – from selection to managing relationships’ hosted by Biocom on March 30, 2021. OncoBone’s talk covered CRO selection, and featured speakers from Inotiv and Aligos Therapeutics continued about partnerships between CROs and Sponsors. Below is a summary of the key aspects covered in the webinar.

There are over 3 000 CROs globally and the number in increasing. The market size is estimated to grow at 12% annual rate and reach 45 billion USD by 2022. About 80% of pharma and biotech representatives see that their use of CRO services is likely to increase.

CROs include large CROs that offer a wide variety of models and services, and niche-providers specialized in certain models or services that are not commonly available. With such large variety and choices, how do you know who to select as your CRO partner? And furthermore, how to invest in a relationship that lasts and brings value to the Sponsor? These topics were discussed on March 30, 2021, in a webinar titled: ‘Working with CROs – from selection to managing relationships’.

Featured speakers in the webinar covered aspects from CRO selection to managing relationships between the CRO and the Sponsor. The speakers represented three different industry sectors. Tiina Kähkönen, Chief Scientific Officer at OncoBone represented a consultant offering CRO selection and management as service, Joe Flynn, Chief Commercial Officer at Inotiv represented a CRO, and Dinah Misner, Senior Director at Aligos Therapeutics represented a pharma company working tightly with CROs.

From selection…

Tiina Kähkönen started the webinar by explaining how to identify eligible CROs that can be considered as a partner in preclinical development. CROs can be found from the internet via web searches or from events/conferences, but most commonly new CROs are referred by colleagues. Referrals typically come from colleagues that have been pleased with the good work of a CRO and the overall client experience that they gained, and these are the key factors for committing to work with the same CRO again.

Joe Flynn referred to a survey which showed that 57% of clients stop buying because they had a better experience elsewhere, and actually 90% of clients say that the experience is as important as the product itself. This also speaks to the fact that while there are many good CROs available that can meet the client’s needs in terms of quality and price, other aspects in the overall service become important when committing to work with a CRO again.

Successful working history can transform the relationship between the Sponsor and the CRO, and the CRO may become a preferred partner for the Sponsor. Dinah Misner discussed Preferred Partner Agreements (PPAs) and their relevance to a pharma company. Issues she saw most important in such agreements were related to the CROs capability to accommodate requested timelines, as well as price reductions based on the quantity of studies that the Sponsor purchases from the CRO. In Dinah’s opinion the PPAs also bring value to CROs as pharma clients are more willing to share their internal timelines and plan their research activities for the following years, which can make it easier for the CROs to predict their operations and gives the CROs the possibility to see through the development process.

One of the questions from the audience was related to how common such PPAs are. Joe speculated that they are rare, with about 5% of clients engaging with such agreements. Joe also explained that over time many clients work with multiple CROs. He explained that this is because clients do not have a clear outsourcing strategy, and on the other hand, CROs may not have a client engagement strategy as they only focus on the projects at hand. Qualifying many CROs can increase flexibility, give access to broader expertise, and give the client better scheduling options, but it also adds expenses, dilutes buying power and reduces commitment.

In selecting a CRO, everything starts with the need for a study with certain key parameters that give a response to the research question at hand. For inquiring information, it is often useful for the client to summarize the information for the CRO in a Request For Proposal that contains all essential information that the CRO needs to be able to prepare a quote for the study. Tiina explained that because many CROs can perform the same study, it is advisable to perform a qualification assessment beyond the capability of performing a study. In these qualifications, many Sponsors see value for example in quality, expertise, communication, stability, timelines and price. Sponsors may value certain attributes differently and outlining the importance of these attributes should be done prior to the CRO evaluation.

Audits can be part of the qualification assessment. One of the questions from the audience was related to audits during the pandemic time. Many audits have been arranged virtually. In practice different types of data rooms have been created to securely share data and other documents, and virtual facility tours have been arranged. Joe also pointed out the possibility of using consultants located in the region of the CRO’s premises who could perform the audits on behalf of the Sponsor without the need for the Sponsor to travel to the site.

After the CRO evaluation has been done, you need to visualize and understand the results, and preparing a summary in the form of a scorecard can be useful. In the evaluation you give scores to all CROs that you have evaluated, and if done correctly, the best scoring CRO should be selected for this specific study. It is important that Sponsors adopt a CRO selection process as it helps them to evaluate the CROs for their best interest, and it also helps in starting to build a relationship with the CRO.

…to managing projects and relationships.

Managing projects means monitoring that everything is performed as agreed. In her presentation, Dinah shared the responsibilities of Sponsor and CRO in this process. The Sponsor’s role is to initiate the study and to support the CRO in performing the study. The Sponsor selects a representative to act as a Study Monitor who will be the primary contact for the study, with responsibilities including scheduling, monitoring the in-life phase and reporting. The Study Monitor communicates with the Study Director, the representative responsible for the study at the CRO.

Joe defined the CRO’s role in the client journey as three steps: teach, tailor and take control. In short, this means discussing and aligning with the client on their needs and conducting the study for them. In fact, taking control is probably the best possible word to describe the process as the CRO does take control for one important part of the client’s drug development process. Dinah also highlighted that CROs are key in supporting drug development for many pharma companies, as only a few companies have the resources to conduct all needed studies in-house.

Communication is key to a successful relationship, and when starting the first project together it is important to share as much information as possible, communicate as openly as possible, and not make any assumptions. One of the questions from the audience was related to communications and how to know if the Sponsor’s and CRO’s definitions of certain terms are the same. There is no simple answer to this, but the best way is to ask for clarification and make sure that you are aligned. Wrong interpretation of terminology can lead to mistakes in projects—and mistakes can lead to adversity. Tiina pointed out that mistakes are often inevitable but when they occur, it is important to communicate respectfully and concentrate on problem solving. Joe pointed out that adversity can, in some cases, strengthen the relationship as solving problems together creates trust; but to survive adversity, it is important to commit to the relationship before it happens.

One of the ways on avoiding adversity and building relationships is to work with the same Study Director within the CRO when possible. Dinah also pointed out that the Study Director knows the research program, and can be better prepared to address any challenges and help in interpreting the results beyond normal input from another Study Director. Furthermore, input from CROs and their Study Directors is important as they have a long history of working, for example, with certain research models and classes of compounds, which helps them in providing insight beyond a specific study.

Investing in relationships is important also from the perspective of a CRO. Joe explained that for a CRO it is 5 times more expensive to get a new client than to keep an existing client, and 71% of clients end the relationship due to bad experience. It’s important for a CRO to know what their clients think of their service and if they are satisfied or not. Joe mentioned that one option is to collect Voice Of Client feedback, which is a good way to improve CRO action. It is also important to follow up with clients for increasing satisfaction and to be able to improve the client’s experience when working with the CRO. Investing in a relationship helps both the CRO and Sponsor in project execution, improves communication and lowers expenses.

Concluding remarks

Adopting a CRO selection process helps in finding valuable partners and managing relationships for the best possible outcome. From a client perspective, expertise and experience are key factors in selecting a CRO, and from a CRO perspective, working together to build trust and strong relationships helps to serve clients better and build continuity of their business.

If you were unable to attend and would like to hear the full webinar, a recording can be found from Biocom’s webpages from the following link.

Upcoming webinar: Human Immune System Models in Metastasis Research

OncoBone and Taconic Biosciences will co-present in a webinar titled: ‘Utility of Human Immune System Mice in Metastasis Cancer Drug Development’ on May 4, 2021. Below is a short overview of what to expect from the webinar.

Immune cells and metastasis

The effects of immune cells, and especially T cells, in regulating tumor growth has received major interest after the successful development and approval of the first immune checkpoint inhibitors for treating multiple cancers. What is not commonly acknowledged is that immune cells also affect other aspects of tumor progression such as metastatic process. Tumor-promoted inflammation makes the tumor microenvironment immunosuppressive, and immune cells regulate metastatic spread by regulating invasion, intravasation, survival of circulating tumor cells, and extravasation to the metastatic microenvironment. During the webinar, OncoBone’s Chief Scientific Officer Tiina Kähkönen will talk about these issues in more detail.

Human Immune System (HIS) mouse models

HIS mouse models are increasingly used in immuno-oncology research and drug development. During the last years, many new HIS models have emerged, all with unique aspects and suitability profiles to answer different research question. Many of these questions are related to what immune cells are present in the model. This is largely affected by the choice of mouse strain and the type of human immune cells that are engrafted in the mice. These and other issues related to HIS model selection will be covered by Taconic’s Field Application Scientist Ivan Gladwyn-Ng.

Value of HIS models in metastasis research and drug development

During the webinar, the utility of HIS models in metastasis research will be discussed, as well as how these models are currently utilized in evaluating approved and emerging immuno-oncology therapies against metastases from the aspects of efficacy and safety. From efficacy aspect, it is discussed how metastases growing at different locations, immune cell landscape, and different compounds targeting the same pathway, can affect the efficacy observed in the models. From safety aspect, increased translational power is discussed, and more precisely how well safety concerns in HIS models are translated to common clinically observed immune-related adverse effects.

Aim of the webinar

In this webinar, we hope to highlight the need of metastasis-specific evaluation of efficacy of novel immunotherapies. Immune responses to metastasis may vary depending on tumor type, stage and local metastatic microenvironment, which makes it more challenging to interpret not only preclinical but also clinical findings. There is a growing demand for further basic and translational research in this field, and development of models with multiple humanized components will be highly valuable. Novel humanized metastasis models will hopefully provide new opportunities for preclinical drug development and assessment of efficacy and safety of immunotherapies, and to promote drug development towards targeting metastases.

More information

The webinar is free to attend, and more information and the registration form can be found from the following link. A webinar recording will be made available for all who have registers to the webinar.

LINK TO REGISTRATION

The webinar is based on the review article: Kähkönen TE, Halleen JM, Bernoulli J. Immunotherapies and metastatic cancers: understanding utility and predictivity of human immune cell engrafted mice in preclinical drug development. 2020. Cancers.

LINK TO FULL TEXT OF REVIEW

More information about HIS models can be found from the following link.

LINK TO HIS MODELS

Experiences on virtual scientific events in 2020 and hopes for 2021

Due to COVID-19 pandemic, the year 2020 has been exceptional in many ways. One of the big drawbacks in biomedical research and business has been that all scientific events were transferred to virtual format. OncoBone representatives attended four virtual scientific events this year. In this blog post we summarize our experiences about them and present our hopes for events organized in 2021.

In-person scientific event typically includes the following activities: 1) preparation to the event (preparing presentation(s) and building itinerary), 2) travel arrangements and traveling, 3) registration, 4) scientific sessions, 5) poster sessions, 6) networking, 7) closing the event (preparing summaries and following up contacts). Notes about these activities in virtual events in 2020 and their comparison to in-person events in earlier years are presented and discussed from our own perspectives and experiences in the following chapters.

Preparation to the events:

Everything from preparing to submitting an abstract and later preparing the presentation(s) (oral or poster) has been the same and required similar amount of time as compared to in-person events. Minor cost saving has been made when no printing is required. Going through the scientific content of the event and building an itinerary has required as much time as in in-person events. However, there has been less content in some of the virtual events in 2020 compared to the same in-person events organized in earlier years.

Traveling:

The biggest change has been cancellation of traveling plans. This has of course the benefit of cost- and time savings, but the difficulty has been the timing of the events. As for a European, the events held in US daylight time have been starting at late afternoon local time and closed sometime after midnight. Truthfully speaking, such late hours are not the best time for learning. Luckily, recordings have been made available so that you can listen to the talks at a more suitable time. However, this has then prevented direct interactions with the presenters and audience, which has only been possible during the live presentations.

Registration and general notes about event administration:

The number of registered participants in virtual events is typically larger compared to in-person events. This is probably because many events have been free or registration has been provided with discounted prices compared to in-person events. However, less time has been spent in the virtual events. The registrants come to the events to listen to topics of their primary interest, and they do not typically listen to other talks outside of their key interest area. Event tough this is a cost-efficient use of working time, learning new science that is not directly related to your primary interest can broaden your view and help in being innovative in your own research.

A notable benefit in scientific events is stepping back from your daily work and busy schedules for a few days and just concentrate on science. As you are attending the virtual events from home or office, you easily switch back to the daily work mode, and in the end you notice that you did not get as much from the events as you had wished for.

One point to note is the change of event dates. Many events have not been held in the announced original time slot that was preserved for the in-person events. This has provided occasionally some difficulties in allocating time for the virtual events.

Arranging virtual events has provided cost savings upon cancellation of reservations of conference centers, which is the major cost in organizing in-person events. However, adaptation to virtual platforms has provided difficulties to the staff members in charge of the events. Many times changing to virtual format has been made on relatively short notice and planning and re-organizing the event has required a lot of time and patience from the organizing committee. I think we are all grateful that it has been possible to change the events to virtual and we have had the opportunity to learn and communicate new science even in these challenging times.

Scientific sessions:

The quality of scientific sessions has been great and it has not been compromised by the change of format. The sessions have been well organized. In some events, an ‘introductory talk’ has been given by a leading scientist in the field prior to the actual scientific session. This is a great way to get your mind settled to a certain topic before detailed cutting-edge scientific discussion. In many scientific sessions, it has been possible to ask questions during the live event and the questions have then been answered in a Q&A session held right after the scientific session. This has been a great way to provide direct feedback and discuss urgent issues (similarly as in in-person events), but the willingness to comment has been less active than in an in-person event.

Poster sessions:

Poster sessions have been well organized and well attended. Actually, some events adopted the use of e-poster format even before these exceptional times, so this concept was not new. However, the lack of good scientific discussions over the posters is a major disadvantage. Also, in virtual format events, you need to only select the posters mainly based on the attractiveness of the title or the results searched with an itinerary builder. In in-person events, when going through the poster presentation area you can accidentally meet people you know or find interesting presentations and have good discussions with the presenters. This kind of spontaneous encounters and discussions are totally lacking in virtual events.

Scientific exchange of results and ideas has decreased and many presentations of new data may have been postponed to future events. This is understandable because discussions at the presentations have typically provided great ideas and new insights into the data, but it is still a pity when thinking about progression and development of science and knowledge.

Networking:

Scientific events are a great platform in reconnecting with old contacts and gaining new. A major disadvantage in virtual format has been the almost complete lack of support for such activities in early virtual formats. Later there has been some attempts to create space for networking. Typically, these activities have been focusing on discussions around a certain scientific topic and sessions have been open to everyone registered to the event. As we see this, many persons are cautious in discussing virtually, especially if they have opposing opinions. To our knowledge, none of the virtual formats can still recapitulate so-called ‘free’ networking space for attendees. By free networking we mean discussing and networking with persons that you accidentally meet for example during a poster session and other discussions you have outside of pre-arranged networking sessions.

Closing of the event:

In a virtual event there should be a better possibility to follow-up with contacts while the event is still ongoing. As every contact occurs online during the event, you already have a line of connection open with the persons you have communicated during the event. In an in-person event such follow-up contacts can usually happen after you have returned home from the event. This is potentially a major advantage of a virtual event. As for preparing meeting summaries about the scientific content of a virtual event, you can always go back and watch the recordings again if you for example notice you are missing some information or would like to include additional content.

Future directions:

Adaptation to everything new in 2020 has been rapid and many changes have been made on short notice. We believe that most of us are happy and grateful for the efforts that have been made for recapitulating the experience of scientific events. However, it is fair to say that people are still anxiously waiting for everything to go back to normal. The biggest drawback at the moment is ‘not knowing’ what will happen next year. It is difficult to make good plans when it is not known if events are going to be held in-person or virtual, if they will be held in the original timelines, and if traveling is allowed. As the restrictions caused by COVID-19 do not seem to ease at least for the first half of 2021, below we present our ‘wish list’ for scientific events in 2021.

The wish list for scientific events in 2021:

  • Considering that it is safe and feasible, in-person events will be the preferred option for all scientific events
  • If in-person events are not the preferred option for all attendees, consider hybrid events where being virtually present is possible for those who prefer it
  • Part of the contents of scientific events, for example educational and keynote lectures, could be posted to everyone, even those not registered to the event. This would allow anyone to evaluate the content of the event virtually for evaluating if the event would be worth registering the next year. This would also be great in the sense of visibility and sharing of science, and it should be available also in in-person events.
  • Provide platforms for ‘free’ networking
  • Contact information of attendees and/or a platform for contacting attendees in electronic format during the event, also in in-person events
  • Access to electronic materials such as posters and exhibitor materials during the event, also in in-person events

How is it like to start a business during COVID-19 crisis

OncoBone offers scientific expertise especially in the fields of oncology and bone diseases. In this blog we discuss and comment new scientific discoveries, new accomplishments in drug development and emerging technologies, and biomedical business -related issues. In this first blog post, we would like to introduce the brief history of OncoBone and share our experience in what it is like to start internationally operating business in Finland during the COVID-19 crisis.

OncoBone was established on January 23, 2020. The company is located in Oulu, Northern Finland.  Just about two weeks before the company was established, on January 10, the World Health Organization (WHO) had given the first warnings of a novel SARS-CoV-2 coronavirus causing pneumonia in Wuhan, China. A week later coronavirus infections were already reported outside China and the disease started to spread uncontrolled. On February 11, the disease was named COVID-19 and active fast-forward moving research on treatment and prevention was started.

To try to control the spread of the disease, meeting and travel restrictions were advised by WHO on February 17, and they were followed on February 26 by advises how to get business ready for COVID-19. Despite the actions and precautions, the virus continued to spread and WHO announced a global pandemic on March 11. By this time, the virus had affected more than 100 countries and over 100 000 people. Soon after, on March 13, Europe became epicenter for the COVID-19 pandemic.

In Finland, COVID-19 started to spread in mid-March, but due to rapid governmental actions and guidance that were well taken and followed, Finland has handled the crisis quite well. Up to August 31, there has been only 8 086 COVID-19 cases in Finland causing 336 deaths.

Businesswise the restrictions have been hard for many companies and due to significant loss of sales during the COVID-19 crisis, a substantial amount of governmental funds have been given to companies that have lost over 30% of revenue compared to the same time last year. According to this criterion, over 200 m€ funding was given to Finnish companies. However, this criterion ruled out all start-up companies who cannot show the required decrease in revenue. This places many companies in a difficult position to carry out their business during these uncertain times, and it is likely that many start-up companies will not survive the COVID-19 crisis. We have personally communicated this to the Ministry of Economic Affairs and Employment in Finland that is responsible for defining the funding criteria, and we hope that the situation will change and there will be funds available for eligible start-up companies also.

For companies operating globally and where the majority of sales and marketing activities are outside Finland, the travel restrictions filed by a martial law in March 16 caused difficulties to new client acquisitions. As for many other companies, we also needed to acquire new platforms to communicate with our international clientele. It has been delighted to notice that despite missing the physical presence, the communication has been excellent. However, it is fair to state that not even the best video conference can be as productive as a face-to-face meeting. Furthermore, the insecure atmosphere with many of our clients has delayed the start of new projects.

A significant change in our business has been that all scientific events have been made virtual. While the virtual events have worked surprisingly well and allowed to gain the latest scientific information, they still lack face-to-face contacts and introductory discussions that are typically needed especially with new contacts.  

Despite the COVID-19 crisis and the delay of projects, OncoBone is in a very good financial position. Together with our own investments we have received a total of 250 k€ funding from our bank Nordea and the governmental institutions Finnvera and ELY-centre, and we would like to sincerely thank them for believing in our business.

Sadly, June 29, 2020 was acknowledged as the six-month anniversary of the COVID-19 outbreak. A lot of effort has been put in research and development to end the crisis. There are more than 200 vaccine candidates in development and currently 7 vaccines in phase 3 clinical trials. The vaccines will most probably be needed for people to feel comfortable in traveling and meeting their colleagues face-to-face.  

OncoBone would like to acknowledge all the healthcare professional and researchers for their current and continuing valuable work to overcome the COVID-19 crisis. We hope that the crisis will be over soon, and it will again be possible to travel to attend scientific and business events and meet our existing and potential clients and other contacts.

We hope to see you all on the road when the situation allows it. Stay safe!

References, cited on August 31, 2020:

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